To achieve an 80% reduction of U.S. GHG emissions by 2050, the DDPP reports state that total CO2 emissions from the entire transportation sector would have to be cut between 75% and 100% from a 2014 baseline. The chapter discusses the role of heavy-duty vehicles (HDVs) and rail in achieving that goal. Freight transportation results in significant GHG emissions. Decarbonizing this sector will require substantial changes to the two primary means of moving freight within the United States: trucking and rail. In particular, emission standards that facilitate fuel efficiency improvements and conversion to zero or near-zero-emission technologies such as electric drivetrain technology, hydrogen, and synthetic gas will likely be necessary to achieve 80% reduction in GHG emissions by mid-century. Moreover, shifting from more fuel-intensive but more flexible transportation modes such as trucking, to more efficient but less flexible modes such as rail can play an important role. In addition to environmental regulation, the significant infrastructure requirements of freight transportation will necessitate federal, state, and local financial investments; changes to regulatory models to encourage more and more-optimal private-sector infrastructure investment; and streamlining of permitting and other barriers. To the extent that new or improved infrastructure is required to expand the rail network or provide fueling or charging infrastructure for advanced technology vehicles, decarbonizing the transportation sector could result in significant job creation in the United States.